The Optimal One-Month Dosing of Lemborexant for Moderate Obstructive Sleep Apnea (OSA) Patients With Low Arousal Threshold

Официальное название

One-Month Dosing of Lemborexant for Treatment of Moderate OSA Patients With Low Arousal Threshold, a Randomized, Double-blind, Crossover, Placebo-Controlled Trial

Обзор

The goal of this clinical trial is to investigate the 1-month treatment effects of different dose of lemborexant in moderate OSA adult patients (18-65 years of age) with low arousal threshold. The main questions it aims to answer are: Primary outcome measure: Apnea/hypopnea index (AHI) Secondary outcome measure: 1. Polysomnography parameters * Mean and nadir oxygen saturation * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency * Rapid eye movement (REM) latency * Percentage of time spent in Non-rapid eye movement (NREM) stage 1-3 and REM stage * Arousal index 2. Oxford Sleep Resistance Test (OSLER) test 3. Epworth Sleepiness Scale (ESS) 4. Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T) 5. Pittsburgh Sleep Quality Index (PSQI) 6. Actigraphy parameters * Total sleep time * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency 7. Sleep diary parameters (Appendix 5) * Total sleep time * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency * Sleep quality Researchers will compare placebo to see if there is a difference in AHI. Participants will * participate a total of 3 phases of study (3-crossover trial) * each phrase the participants will receive either lemborexant 5 mg, lemborexant 10 mg, or placebo orally per day for 30 days with 2-week washout (depend on intervention arm whether the participants receive which intervention sequence) * complete three overnight in-laboratory polysomnography (2-week washout) at day 30 of each phrase * monitor actigraphy during day 1 to 29 of intervention of all periods * record sleep diary during day 1 to 29 of intervention of all periods * complete the OSLER test in the morning of the three overnight test * complete questionnaires including: Epworth Sleepiness Scale (ESS), Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T), Pittsburgh Sleep Quality Index (PSQI) at baseline (prior to intervention) and the night before overnight in-laboratory polysomnography

Вмешательства

• Препарат Lemborexant 5 MG [Dayvigo] Period 1
  Participants will receive lemborexant 5 mg per day for 30 days during first period
• Препарат Placebo Period 1
  Participants will receive placebo 5 mg per day for 30 days during the first period
• Препарат Lemborexant 5 MG [Dayvigo] Period 2
  Participant will receive lemborexant 5 mg per day for 30 days during the second period
• Препарат Placebo Period 2
  Participant will receive placebo 5 mg per day for 30 days during the second period
• Препарат Lemborexant 5 MG [Dayvigo] Period 3
  Participants will receive lemborexant 5 mg per day for 30 days during third period
• Препарат Placebo Period 3
  Participants will receive placebo per day for 30 days during third period
• Препарат Lemborexant 10 MG [Dayvigo] Period 1
  Participants will receive lemborexant 10 mg per day for 30 days during first period
• Препарат Lemborexant 10 MG [Dayvigo] Period 2
  Participants will receive lemborexant 10 mg per day for 30 days during second period
• Препарат Lemborexant 10 MG [Dayvigo] Period 3
  Participants will receive lemborexant 10 mg per day for 30 days during third period

Первичные конечные точки

• Apnea/hypopnea index (AHI) [Срок оценки: At day 30 during the overnight in-laboratory of each study period]

Вторичные конечные точки (12)

• Mean and nadir oxygen saturation [Срок оценки: At day 30 during the overnight in-laboratory of each study period]
• Sleep efficiency [Срок оценки: At day 30 during the overnight in-laboratory of each study period]
• Wake after sleep onset (WASO) [Срок оценки: At day 30 during the overnight in-laboratory of each study period]
• Sleep latency [Срок оценки: At day 30 during the overnight in-laboratory of each study period]
• REM latency [Срок оценки: At day 30 during the overnight in-laboratory of each study period]
• Percentage of time spent in NREM stage 1-3 and REM stage [Срок оценки: At day 30 during the overnight in-laboratory of each study period]
• Arousal index [Срок оценки: At day 30 during the overnight in-laboratory of each study period]
• OSLER error index [Срок оценки: On the morning of the in-laboratory polysomnography]
• Epworth Sleepiness Scale (ESS) [Срок оценки: Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period]
• Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T) [Срок оценки: Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period]
• Pittsburgh Sleep Quality Index [Срок оценки: Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period]
• Total sleep time [Срок оценки: During day 1-29 of intervention]

Критерии участия

Критерии включения

Individuals are eligible for participation in this study if they have all of the followings:

• Patient, aged 18 - 65 years at the time of informed consent
• Voluntary agreement and capable for giving written informed consent
• Diagnosis with OSA according to the criteria of the International Classification of Sleep Disorders, version 3 Text Revision
• Baseline screening polysomnography (PSG) demonstrated apnea-hypopnea index 15 - 30 events/h of sleep (moderate severity)
• Patients identified as low arousal threshold using previously recommended criteria which allocated a score of 1 to each criterion: apnea-hypopnea index < 30 events per hour, nadir oxygen saturation as measured by pulse oximetry > 82.5%, and fraction of hypopneas > 58.3%. A score of 2 or above defined a low arousal threshold.
• Peripheral capillary oxygen saturation (SpO2) ≥ 94% measured during screening visit
• Habitually sleeping ≥ 5.5 hours/night with usual bedtime falls within the range of 9:00 PM to 1:00 AM
• Body mass index 18 - 40 kg/m2 Exclusion criteria

Individuals were not eligible for participation in this study if they have any of the followings:

• Previous allergy or adverse effects with Lemborexant or other sedatives
• Pregnant or breastfeeding
• Significant medical comorbidities that could affect individual safety and study assessment results, regarding investigators' opinion
• Uncontrolled cardiovascular or cerebrovascular diseases
• Neuromuscular diseases
• Nasal anatomical defect
• Significant psychiatric comorbidities that could affect individual safety and study assessment results, regarding investigators' opinion
• Active respiratory disorders other than OSA
• Central respiratory events (CAHI) >25% of the total AHI
• Diagnosis/symptoms of sleep-related disease other than OSA including narcolepsy, restless legs syndrome, periodic limb movement disorder, or circadian rhythm sleep-wake disorder
• Severe hypersomnolence (ESS ≥16)
• Peripheral capillary oxygen saturation (SpO2) < 80% for ≥ 5% of total sleep time measured during screening visit
• Driving-related sleepiness accident or near misses in the past 12 months
• Safety-critical occupation
• Using CPAP or other dental devices within 2 weeks of screening polysomnography until the end of the study
• Unable to tolerate equipment in this study
• Taking any medication that affects sleep or other variable measured in this study
• Taking any medication with cytochrome P450 Family 3A (CYP3A) inhibitors and all CYP3A inducers
• Drug or alcohol use disorder within 2 years before the study initiation or current excessive alcohol intake
• Excessive caffeine intake

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Таиланд · 1 центр

• Chulalongkorn University — Pathum Wan

Идентификаторы

NCT: NCT07683442 · 0594/69

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗